Inside The Cell, Experts See Life's Origin

Published: April 6, 1999

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Both Dr. Cech and Dr. Orgel, a leading authority on the origin of life, suggest that there was a pre-RNA world, in which the starring role was played by some other self-replicating, catalytic molecule.

''We don't know what it was but we are looking,'' Dr. Orgel said.

Alternative genetic systems are now being studied. One, known as pyranosyl-RNA, has a six-atom ring in place of the five-atom ring of ordinary ribose. Another, called peptide nucleic acid, has the same chemical backbone as proteins but with nucleic acid bases in place of protein's usual amino acid side-chains.

Both pyranosyl-RNA and peptide nucleic acid display the behavior to be expected of a genetic molecule, such as linking together in double chains like the double helix of DNA.

''If you want DNA-like double helices, there are probably scores'' of molecules that would serve as genetic systems, Dr. Orgel said. ''It raises the question of why we have RNA and DNA instead of others that are equally good.''

The idea of a pre-RNA world creates many possibilities for researchers exploring prebiotic reactions, the chemistry that led to the first living entities. But in some ways it sets the search for the origin of life back to square one. Pyranosyl-RNA and peptide nucleic acid may be promising candidates, but no one yet knows if their spontaneous formation is any more plausible than that of RNA.

The concept of the RNA world is also unproven in its central assertion, that an RNA molecule could catalyze its own replication. The natural RNA catalysts found today sponsor quite simple chemical reactions. Chemists like David P. Bartel of the Whitehead Institute in Cambridge, Mass., have been trying to construct RNA molecules with a more extensive repertoire. Some RNA's show promising behavior such as being able to copy a short stretch of another RNA. But that is a far cry from a self-copying molecule.

''No one has come close to getting a self-replicating RNA,'' Dr. Bartel said. ''It's a long road. It would be exciting to get an RNA that can copy a complete turn of the helix.''

Another worry for prebiotic chemists is the possibility that they may run out of time. Scientists once thought that a billion years or so elapsed before the first appearance of life on earth. But the earliest date that life could have started has been pushed forward by planetary astronomers. They believe that debris left over from the early solar system would have continued to bombard the earth long after the planet's formation some 4.6 billion years ago. The larger of these impacts would have boiled off the early oceans into steam, sterilizing the planet of any life forms that might have emerged.

The primeval bombardment is thought to have ceased some four billion years ago. Meanwhile, fossil hunters have steadily pushed back the date by which life must have started by finding ever older fossils. The earliest known fossils exist in rocks that are 3.85 billion years old, leaving a mere 150 million years for life to have started.

This sharply narrower window is not yet an intellectual embarrassment -- a lot can happen in 150 million years. Still, the shrinking window worries the eminent theoretician of molecular biology, Francis H. C. Crick.

In a foreword to the first edition of ''The RNA World,'' written when the oldest known fossils were a mere 3.6 billion years old, Dr. Crick said that the available window ''leaves an astonishingly short time to get life started.'' He also noted that the three kingdoms of early life -- bacteria, the bacteria-like microbes known as archaea, and the plant and animal kingdom -- ''seem a very long distance from their hypothetical common ancestor.''

Dr. Crick then proposed that life might have started elsewhere in the universe, maybe on a planet whose chemical environment was more conducive to the genesis of life than was Earth's. The three kingdoms might represent the survivors of an assortment of microbes sent to colonize distant planets.

Dr. Crick's speculation that life originated elsewhere would provide an escape hatch for scientists trying to explain the origin of life on earth should the available window of time be squeezed implausibly short. So far the idea has few takers, but nor is it being dismissed out of hand.

Dr. Orgel believes there is no way of assessing the probability of life or how many years may have been required for its emergence. ''It's hard to say whether the origin of life took a million years or a billion,'' he said. ''I don't think there is anything to be concerned about unless there were organisms extant before the earth became inhabitable. That would be a real puzzle.''

Dr. Cech agrees that life on earth got started astonishingly quickly, but still looks to explain that process in terrestrial terms. ''While extraterrestrial origins cannot and should be discounted -- a lot of organic material certainly came in via comets, for example -- it may not be necessary to invoke 'visitors from outer space,' '' he said.

In an experiment of 1953, still taught in every textbook, Stanley Miller showed that several of the principal chemicals of life could be formed by running an electrical discharge (lightning) through a flask of air and water (atmosphere and ocean). At once the problem of the origin of life seemed soluble in principle. But Dr. Miller's brilliant experiment has proved something of a dead end; no one has managed to take it much further.

The concept of the RNA world may be the best available scenario of how life started, but as with Dr. Miller's experiment, it has proved frustratingly difficult to take a promising idea further. ''It would be unhealthy not to have doubts,'' Dr. Cech said. ''Scientists are good at checking things in the lab, but this is a historical question and there is no videotape to document what happened.''

However soluble the mystery of life's origins may seem in principle, it remains very far from solution.

Chart: ''Best Scenario for Origin of Life'' Life presumably evolved from the simple chemicals present on the primitive earth some four billion years ago. The most likely scenario focuses on ribonucleic acid, or RNA, a sub-stance that performs many vital tasks in living cells today. Nucleotides, the building blocks of RNA, consist of the sugar known as ribose (R), attached to phosphate (P) and to a base (B). Each of these three components can be made from simple chemicals like formaldehyde, hydrogen cyanide and ammonia. The probability that RNA molecules formed spontaneously on the primitive earth seems very small at present. Maybe some other molecule gave rise to RNA. But once in existence, an RNA molecule could both store infor-mation and make copies of itself. The self-copying RNA molecules somehow acquired a cell membrane. The information-storage task was handed off to DNA and the job of catalyzing chemical reactions passed to proteins. RNA continued many data processing tasks. Today's cells are run by the troika of RNA, DNA and protein. (pg. F4)